Gain of 3q26: A genetic marker in low-grade squamous intraepithelial lesions (LSIL) of the uterine cervix

Abstract

Objective Physicians have few resources for determining which LSIL will progress to HSIL or regress. Recently the chromosome 3q26 region was found to be amplified in patients with cervical cancer. The frequency of this 3q gain increased with severity of dysplasia. The primary objective of this study was to evaluate an automated FISH assay for detection of 3q gain in liquid cytology samples as a potential tool for risk stratification and triaging. Methods Slides prepared from 257 liquid cytology specimens (97 Negative, 135 LSIL 25 HSIL) were hybridized with a single-copy probe for the chromosome 3q26 region and a probe for the centromeric alpha-repeat sequence of chromosome 7, using standard FISH methods. Using automated analysis, the total number of nuclei and the number of nuclei with > 2 signals for 3q26 were determined, using a 20× objective. The nuclei were rank ordered based on number of 3q26 FISH signals. The 800 nuclei with the highest number of signals were scored using both FISH probes and nuclei with increased numbers of 3q signals were enumerated. Results and conclusions Analysis of 257 specimens demonstrated that a fully automated FISH scoring system can detect 3q gain in liquid cytology samples. A fully automated method for determination of 3q gain in liquid cytology may be the assay necessary to implement routine testing. Additional studies to validate the utility of this technology are needed.